Faculty Collaboration Database

Studies of the role of membrane lipid order in the effects of delta 9-tetrahydrocannabinol on adenylate cyclase activation in heart. J Pharmacol Exp Ther 1990 Mar;252(3):1075-82

Date

03/01/1990

Pubmed ID

2156989

Scopus ID

2-s2.0-0025257436 (requires institutional sign-in at Scopus site)   26 Citations

Abstract

The studies in this report were carried out to investigate the effects of delta 9-tetrahydrocannabinol (delta 9-THC) on cardiac membrane adenylate cyclase activity and to determine the role of changes in membrane lipid order in these effects. delta 9-THC and its psychoactive metabolite, 11-OH-delta 9-THC, increased isoproterenol (ISO) stimulation of adenylate cyclase in rat cardiac ventricular membranes. Cannabidiol, cannabinol and (+)-delta 9-THC were all without effect, indicating that this effect of delta 9-THC is stereoselective and specific for cannabinoids with psychoactive potency. delta 9-THC also increased glucagon stimulation of adenylate cyclase. The enhancement of both ISO and glucagon-stimulated adenylate cyclase was due to an increase in the Vmax of these agonists with no significant change in Kact. delta 9-THC did not affect basal adenylate cyclase activity or the activation of the enzyme by forskolin, guanine nucleotides or fluoride ion. Those cannabinoids which increased ISO-stimulated adenylate cyclase activity also decreased the break temperature of the Arrhenius plot; evidence that the effects of delta 9-THC involve changes in membrane phospholipid order. The effects of the cannabinoids on cardiac membrane phospholipid order were investigated directly using diphenylhexatriene fluorescence polarization. delta 9-THC and 11-OH-delta 9-THC alone decreased the break temperature of the diphenylhexatriene temperature profile, i.e., decreased the temperature of the lipid phase separation. This effect of delta 9-THC was stereoselective.(ABSTRACT TRUNCATED AT 250 WORDS)

Author List

Hillard CJ, Pounds JJ, Boyer DR, Bloom AS

Author

Cecilia J. Hillard PhD Associate Dean, Center Director, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adenylyl Cyclases
Animals
Colforsin
Dronabinol
Enzyme Activation
Heart
In Vitro Techniques
Male
Membrane Lipids
Myocardium
Rats
Rats, Inbred Strains
Stereoisomerism